Schiffrin E L
Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada.
Curr Opin Cardiol. 1995 Sep;10(5):485-94.
The endothelins, 21-amino-acid peptides produced by the endothelium of blood vessels and many other tissues such as the kidney, brain, endocrine organs, etc., are potent vasoconstrictors, and are also endowed with mitogenic and cell hypertrophic properties. Endothelin may be involved in the pathogenesis of hypertension through vascular, renal, endocrine, and neural effects. Although many studies have been performed to test the hypothesis that these peptides have a pathophysiologic role in hypertension, it is only recently that evidence has been found of enhanced production of endothelin-1 in some models of hypertension, particularly in blood vessels in deoxycorticosterone acetate-salt hypertensive rats. Vascular responses to endothelin-1 have been shown to be normal or depressed in many models of experimental hypertension, and also in humans with essential hypertension. Elevation of blood pressure and development of vascular hypertrophy is blunted in deoxycorticosterone acetate-salt hypertensive rats treated chronically with endothelin receptor antagonists. Spontaneously hypertensive rats do not overexpress vascular endothelin, and do not exhibit a hypotensive response to chronic endothelin receptor antagonism. Malignant spontaneously hypertensive rats treated with deoxycorticosterone acetate and salt exhibit vascular overexpression of endothelin-1 and respond to endothelin antagonists with lowering of blood pressure. A genetic role of components of the endothelin system has been suggested in Dahl salt-sensitive rats. In human essential hypertension, there is as yet little evidence of activation of the endothelin system. A role of endothelins in hypertension is thus becoming increasingly apparent in severe forms of experimental hypertension, but further studies are required to establish whether these peptides are involved in the human disease.
内皮素是由血管内皮以及肾脏、脑、内分泌器官等许多其他组织产生的21个氨基酸的肽，是强效血管收缩剂，还具有促有丝分裂和细胞肥大特性。内皮素可能通过血管、肾脏、内分泌和神经作用参与高血压的发病机制。尽管已经进行了许多研究来检验这些肽在高血压中具有病理生理作用的假说，但直到最近才在一些高血压模型中发现内皮素-1产生增加的证据，特别是在醋酸脱氧皮质酮-盐高血压大鼠的血管中。在许多实验性高血压模型以及原发性高血压患者中，血管对内皮素-1的反应已被证明是正常的或减弱的。长期用内皮素受体拮抗剂治疗的醋酸脱氧皮质酮-盐高血压大鼠，血压升高和血管肥大的发展受到抑制。自发性高血压大鼠不过度表达血管内皮素，对慢性内皮素受体拮抗作用也不表现出降压反应。用醋酸脱氧皮质酮和盐治疗的恶性自发性高血压大鼠表现出血管内皮素-1的过度表达，并对内皮素拮抗剂产生血压降低反应。在 Dahl 盐敏感大鼠中已提示内皮素系统成分的遗传作用。在人类原发性高血压中，尚无内皮素系统激活的证据。因此，内皮素在高血压中的作用在严重形式的实验性高血压中越来越明显，但需要进一步研究来确定这些肽是否参与人类疾病。
